Kineret, anakinra

The following drug information is obtained from various newswires, published medical journal articles, and medical conference presentations.

Approval Status:

Approved January 2013

Specific Treatments:

Cryopyrin-Associated Periodic Syndromes

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General Information

Kineret (anakinra) is an intravenous recombinant, nonglycosylated form of human interleukin-1 receptor antagonist (IL-1Ra). It blocks the biologic activity of IL-1 alpha and beta by competitively inhibiting IL-1 binding to the interleukin-1 type I receptor (IL-1RI), which is expressed in a wide variety of tissues and organs. IL-1 production is induced in response to inflammatory stimuli and mediates various physiologic responses including inflammatory and immunological responses.

Kineret is specifically indicated for Neonatal-Onset Multisystem Inflammatory Disease, a severe form of Cryopyrin-Associated Periodic Syndromes.

Kineret is supplied as a solution for subcutaneous injection. The recommended starting dose is 1-2 mg/kg. The dose can be individually adjusted to a maximum of 8 mg/kg daily to control active inflammation.

Clinical Results

FDA Approval
The FDA approval of Kineret was based on a long-term, open-label and uncontrolled study. This study included 43 NOMID patients 0.7 to 46 years of age who were given an initial Kineret dose of 1 to 2.4 mg/kg body weight. During the study, the dose was adjusted by 0.5 to 1 mg/kg increments to a protocol-specified maximum of 10 mg/kg daily, titrated to control signs and symptoms of disease. The maximum dose studied was 7.6 mg/kg/day. The average maintenance dose was 3 to 4 mg/kg daily. In general, the dose was given once daily, but for some subjects, the dose was split into twice daily administrations for better control of disease activity. The subjects were treated for up to 60 months. NOMID symptoms were assessed with a disease-specific Diary Symptom Sum Score (DSSS), which included the prominent disease symptoms fever, rash, joint pain, vomiting, and headache. Improvements occurred in all individual disease symptoms comprising the DSSS, as well as in the serum markers of inflammation. Results were consistent across all subgroups, including age, gender, presence of CIAS1 mutation, and disease phenotype. For 11 patients who went through a withdrawal phase, disease symptoms and serum markers of inflammation worsened after withdrawal and promptly responded to reinstitution of Kineret therapy. Upon withdrawal of treatment, the median time until disease flare criteria were met was 5 days.

Side Effects

Adverse events associated with the use of Kineret for NOMID may include, but are not limited to, the following:

  • injection site reaction
  • headache
  • vomiting
  • arthralgia
  • pyrexia
  • nasopharyngitis

Mechanism of Action

Kineret (anakinra) is an intravenous recombinant, nonglycosylated form of human interleukin-1 receptor antagonist (IL-1Ra). It blocks the biologic activity of IL-1 alpha and beta by competitively inhibiting IL-1 binding to the interleukin-1 type I receptor (IL-1RI), which is expressed in a wide variety of tissues and organs. IL-1 production is induced in response to inflammatory stimuli and mediates various physiologic responses including inflammatory and immunological responses. Spontaneous mutations in the CIAS1/NLRP3 gene have been identified in a majority of patients with cryopyrin-associated periodic syndromes such as NOMID. CIAS1/NLRP3 encodes for cryopyrin, a component of the inflammasome. The activated inflammasome results in proteolytic maturation and secretion of IL-1ß, which has an important role in the systemic inflammation and manifestations of NOMID.

Literature References

Neven B, Marvillet I, Terrada C, Ferster A, Boddaert N, Couloignier V, Pinto G, Pagnier A, Bodemer C, Bodaghi B, Tardieu M, Prieur AM, Quartier P Long-term efficacy of the interleukin-1 receptor antagonist anakinra in ten patients with neonatal-onset multisystem inflammatory disease/chronic infantile neurologic, cutaneous, articular syndrome. Arthritis and Rheumatism 2010 Jan;62(1):258-67

Additional Information

For additional information regarding Kineret or Cryopyrin-Associated Periodic Syndromes, please visit the Kineretrx web page.